Role of IL-6, sIL-6R, IL-1 beta, TNF-alpha, and B2M in pathophysiology and prognosis of multiple myeloma

ABSTRACT

Cytokines control myeloma cell proliferation, differentiation, apoptosis and tumor-induced bone marrow destruction. The present study was designed to estimate the serum levels of interleukin-6 [IL-6], soluble IL-6 receptor [sIL-6R], IL-1 beta, tumor necrosis factor-alpha [TNF-alpha], and beta-2 microglobulin [beta 2M] in multiple myeloma [MM] in an attempt to elucidate their role in the disease, to study their levels in different immunologic types of MM, and to evaluate the effect of therapy on these levels. The study included 40 patients with MM, 20 newly diagnosed [group I] and 20 patients receiving treatment [group II]. Ten patients received therapy for patients received therapy for > one year [group IIb]. Patients were subclassified according to beta 2M level into [patients with beta 2M < 6 mg/L and patients with beta 2M >/= 6 mg/L]. Fifteen healthy individuals were included as controls. Samples of all patients and controls were subjected to serum protein electrophoresis, immunofixation, serum cytokines [IL-6, IL-1 beta, TNF-alpha], sIL-6R, and beta 2-microglobulin estimation. Bone marrow aspiration [for patients only] and other laboratory chemical investigations were also performed. Serum immunofixation electrophoresis revealed that out of 40 patients, 25 were IgG myeloma, 12 were IgA myeloma, one case was light chain myeloma and 2 cases had biclonal gammopathy. Serum IL-6, sIL-6R, IL-1 beta, TNF-alpha and beta 2M showed significant increase in patient groups compared to controls, with no significant difference between groups I and II in both [IgG] and [IgA] myeloma. On the other hand, IL-6, sIL-6R, and beta 2M were significantly decreased in group IIb when compared with group I and group IIa. When beta 2M level was used for subgrouping, IL-6, sIL-6R, IL-1 beta, and TNF-alpha were significantly higher in group II patients with beta 2M >/= 6 mg/L than those with beta 2M < 6 mg/L. As IL-6, sIL-6R, IL-1 beta TNF-alpha, and beta 2M were elevated in all the studied myeloma patients, they might be involved in the pathophysiology of the disease irrespective of its immunologic type. IL-6 and sIL-6R could be used in monitoring the effect of therapy in MM especially in patients with impaired renal function. In addition of being known as a good prognostic marker, beta 2M could be used to monitor the response to therapy in MM